ABSTRACT The goal of this application is to develop an antimicrobial tracheostomy tube (TT) to reduce infections associated with tracheostomies and prolonged mechanical ventilation (PMV). Approximately 100,000 patients undergo a tracheotomy each year in the US.1 About 5000 of these patients are children, making it one of the most common pediatric surgical airway procedures.2 The number of tracheostomies in children has increased substantially in recent years and is expected to continue to rise, largely due to an increase in survival of children born prematurely and with chronic disorders. Tracheostomy related infections are common and include stoma cellulitis, tracheitis, and bacterial pneumonia, including ventilator associated pneumonia (VAP). In children that receive a tracheostomy and are discharged with a TT in place, 17% have an unplanned hospital readmission within 30 days and over 40% are readmitted within one year for bacterial tracheostomy associated respiratory tract infection (bTARTI).3, 4 Biofilms form rapidly on TTs and harbor bacteria that are resistant to antibiotics and the patient?s immune system. These biofilms contribute to infections and the persistence of infections under treatment, especially in patients dependent on PMV. Although problems associated with biofilm formation on TTs have been clearly identified, today there are no antimicrobial TTs available. We hypothesize that preventing biofilm formation on TTs will improve their safety and function and believe that there is a substantial commercial opportunity to address this unmet need. The Phase II scope of work builds on strong Phase I results that established the ability to coat PVC based tracheal tubes with a novel formulation of an engineered antimicrobial peptide. Coated devices were effective at preventing biofilm formation by multidrug resistant pathogens and were biocompatible in cytotoxicity studies. The coated ETTs were also shown to be mechanically durable and remained stable/active post sterilization. Phase II objectives include (1) optimizing the coating formulation, (2) developing pilot scale coating process requirements, (3) evaluating safety and efficacy in a large animal model, (4) completing biocompatibility and bench testing, and (5) completing a pre-submission meeting with FDA. Success of this project is expected to have a significant impact on the safety and quality of life of tracheostomized patients and their families by preventing ventilator associated pneumonia and unplanned hospital readmissions due to respiratory tract infections. This has high potential to reduce treatment cost. It may also reduce the number of patients requiring antibiotic therapy and, in this way, help preserve the efficacy of front line clinical antibiotics.